Virology Journal最新文献

Varicella-zoster virus (VZV) is the etiological agent of chickenpox and shingles, diseases characterised by epidermal virus replication in skin and mucosa and the formation of blisters. We have previously shown that VZV infection has a profound effect on keratinocyte differentiation, altering the normal pattern of epidermal gene expression. In particular, VZV infection reduces expression of suprabasal keratins 1 and 10 and desmosomal proteins, disrupting epidermal structure to promote expression of a blistering phenotype. Here, we extend these findings to show that VZV infection upregulates the expression of keratin 15 (KRT15), a marker expressed by basal epidermal keratinocytes and hair follicles stem cells. We demonstrate that KRT15 is essential for VZV replication in the skin, since downregulation of KRT15 inhibits VZV replication in keratinocytes, while KRT15 exogenous overexpression supports viral replication. Importantly, our data show that VZV upregulation of KRT15 depends on the expression of the VZV immediate early gene ORF62. ORF62 is the only regulatory gene that is mutated in the live attenuated VZV vaccine and contains four of the five fixed mutations present in the VZV Oka vaccine. Our data indicate that the mutated vaccine ORF62 is not capable of upregulating KRT15, suggesting that this may contribute to the vaccine attenuation in skin. Taken together our data present a novel association between VZV and KRT15, which may open a new therapeutic window for a topical targeting of VZV replication in the skin via modulation of KRT15.

Although COVID-19 is a disease consisting of mostly upper and lower respiratory symptoms, a subset of patients develop cardiac sequelae including myocarditis and pericarditis. For these patients, a standardized set of diagnostic imaging techniques and treatments has not been established. While there have been numerous case reports on this topic, there are few reviews that evaluate the effectiveness of different treatment modalities with a significant number of cases. We reviewed 146 cases of patients (ages ranging from 2 months old to mid 80 s) obtained from searches on PubMed, Google Scholar, and several case report journals. ECG abnormalities, elevated inflammatory markers, and reduced left ventricular ejection fraction were most associated with COVID-19 myocarditis. While classic symptoms of COVID-19 include upper respiratory symptoms, a subset of patients diagnosed with COVID-19 displayed no signs of respiratory disease at all. In 22% of cases, cardiac sequelae was not present until after the patient recovered from COVID-19. Steroids were given in 57.5% of cases. Cardiac MRI was used in 40.4% of cases for diagnosis of myocarditis. Of all the patients who were treated with ECMO, 82.1% of these patients were able to fully recover. The use of cardiac MRI and transthoracic echocardiogram for diagnosis of COVID-19 myocarditis should be heavily considered in any patient with COVID-19 infection. ECMO, IVIG, steroids, and anticoagulants should also be heavily considered. A randomized controlled trial should be conducted to better associate treatments with outcomes.

Background: Common cold coronaviruses (ccCoVs) and influenza virus are common infectious agents causing upper respiratory tract infections (RTIs). However, clinical symptoms, comorbidities, and health effects of ccCoV infection remain understudied.

Methods: A retrospective study evaluated 3,935 outpatients with acute upper RTI at a tertiary teaching hospital. The presence of ccCoV and influenza virus was determined by multiplex molecular assay. The demographic, clinical symptoms, and health outcomes were compared between patients with ccCoV (n = 205) and influenza (n = 417) infections. Multivariable logistic regression was employed to evaluate predictors and health outcomes over a one-year follow-up.

Results: Sore throat, nasal discharge, headache, and myalgia were more predominant in ccCoV infection; fever was common in influenza. Most patients reported moderate symptoms severity (49.8% ccCoV, 56.1% influenza). Subsequent primary care visits with symptoms of RTI within a year were comparable for both infections (27.3% ccCoV vs. 27.6% influenza). However, patients with influenza reported increased primary care visits for non-RTI episodes and all-cause hospital admission. Baseline comorbidities were associated with increased primary care visits with symptoms of RTI in either ccCoV (adjusted odds ratio [aOR] 2.5; 95% confidence interval [CI] 1.1-5.9; P = 0.034) or influenza (OR 1.9; 95% CI 1.1-3.1; P = 0.017) infections, due probably to the dysregulation of the host immune response following acute infections. In patients infected with influenza infection, dyslipidemia was a predictor for subsequent primary care visits with symptoms of RTI (unadjusted OR 1.8; 95% CI 1.0-3.0; P = 0.040).

Conclusions: Both influenza and ccCoV infection pose significant disease burden, especially in patients with comorbidities. The management of comorbidities should be prioritized to mitigate poor health outcomes in infected individuals.

Background: Human adenoviruses (HAdVs) frequently cause common respiratory or gastrointestinal infections among children, adults, individuals with immune deficiencies, and other vulnerable populations with varying degree of symptoms, ranging from mild to server, and in some cases, even fatalities. Despite the significant clinical impact of HAdVs, there is currently no approved vaccine available.

Methods: This study explores the potential of the adenovirus type 5 fiber knob (Ad5-FK) to stimulate the production of Ad-specific neutralizing antibodies and T-cell responses in mice. Based on structure predictions, we first expressed Ad5-FK in E. coli and confirmed the assembly of FK into its trimeric form. After testing the binding capability of the trimeric FK to susceptible cells, the immunogenicity of the protein in combination with the c-di-AMP adjuvant was assessed in BALB/c mice.

Results: The purified Ad5-FK exhibited self-trimerization and maintained correct conformation akin to the authentic FK structure. This facilitated effective binding to susceptible HEK293 cells. Notably, the protein demonstrated significant inhibition of HEK293 cells infection by rAd5-GFP. Immunization of BALB/c mice with Ad5-FK, or Ad5-FK mixed with c-di-AMP yielded FK-specific antibodies with potent neutralization capacity. Significantly, Ad5-FK was found to elicit a vigorous CD4⁺ T-cell response in the immunized mice.

Conclusion: Our findings underscore the efficacy of FK-based vaccine in eliciting anti-Ad humoral immune response and CD4 T-cell immune reactions essential for protection against viral infections.

The research was conducted in Jimma town, Oromiya Regional State, from October 2022 to June 2023, with the aim of assessing the immune response of polyvalent FMD (Foot and Mouth Disease) vaccine. The study involved 34 cattle in a longitudinal study, divided into two groups: 29 vaccinated and 5 unvaccinated. The vaccinated cattle received an inactivated polyvalent FMD virus vaccine produced by the National Veterinary Institute. Blood samples were collected on days 0, 14, 21, 35, 80, and 125 after vaccination and tested using Virus Neutralization Test and 3ABC ELISA. The results showed a significant increase in neutralizing antibodies against structural proteins in all vaccinated cattle on day 14 after vaccination for all three serotypes. (A/ETH/21/2000, p = 0.015; O/ETH/38/2005, p = 0.017; SAT2/ETH/64/2009, p = 0.007). On day, fourteen of post-vaccination vaccinated group showed immune response equal or above 1.5 log10 in a proportion of 69%, 73% and 94% for serotype A/ETH/21/2000, O/ETH/38/2005 and SAT2/ETH/64/2009 respectively. The status of raised antibody titer on day 125 post-vaccination showed decreasing by 14%, 18% and 4% for serotype A/ETH/21/2000, O/ETH/38/2005 and SAT2/ETH/64/2009 respectively. The DIVA test, or 3ABC ELISA, used to differentiate infected from vaccinated animals, revealed the absence of immune response to the Non-structural protein in the vaccinated cattle group. Conversely, the unvaccinated group showed no recorded antibody titer to both structural and non-structural proteins. In summary, the commercially available FMD vaccine, comprising serotype A, O, and SAT2, triggers an immune response to the structural protein rather than the non-structural protein after the initial administration. This outcome implies that FMD vaccines from the National Veterinary Institute align with the DIVA test. Nevertheless, additional efforts may be necessary to bolster the strength and duration of the vaccine-induced immune response.

Background: SARS-CoV-2 viremia is associated with disease severity and high risk for in-hospital mortality. However, the impact of SARS-CoV-2 viremia on long-term outcomes in hospitalized patients with COVID-19 is poorly understood.

Methods: We conducted a prospective cohort study and recruited a group of older adult patients with COVID-19 admitted to pulmonary intermediate care units of Peking University Third Hospital during December 2022 and January 2023. The plasma level of SARS-CoV-2 RNA was determined by a standardized RT-PCR technique, and SARS-CoV-2 RNAemia was defined as a plasma viral load ≥ 50 copies/ml. In-hospital and follow-up (180-day) outcome data were collected.

Results: A total of 101 patients with an average of 80.4 years were recruited, and 63.4% of them were severe or very severe cases. Twenty-eight patients (27.7%) had SARS-CoV-2 RNAemia, with a median viral RNA load of 422.1 [261.3, 1085.6] copies/ml. Patients with SARS-CoV-2 RNAemia were more likely to develop critical cases and had a higher incidence of sepsis. Accordingly, they had a higher 180-day mortality (57.1% vs. 19.7%, P < 0.001), as well as in-hospital mortality (50.0% vs. 13.7%, P < 0.001), independent of age, disease severity, sepsis, lymphocyte count and C-Reactive protein. In addition, the risk for 180-day mortality increased with the SARS-CoV-2 RNA load in plasma. Plasma cytokines, including IL-6, IL-8 and IL-10, were higher in patients with SARS-CoV-2 RNAemia.

Conclusions: Our study indicates that SARS-CoV-2 RNAemia serves as a useful biomarker for predicting mortality, especially long-term mortality, in older adult patients hospitalized in pulmonary intermediate care units.

Trial registration: Chinese Clinical Trial Registry website (No. ChiCTR2300067434).

Background: Human papillomavirus (HPV), is one of the main causes of cervical cancer and also one of the most common sexually transmitted infections (STIs). HPV is responsible for almost all cases of cervical cancer and plays a principal role in causing other cancers including oropharynx, penis, larynx, oral cavity, anus, vulva, and vagina. The study aims to investigate the prevalence and distribution of HPV genotypes among patients referred to private laboratories in Mashhad, located in the northeast of Iran.

Methods and materials: 428 samples including 382 females (89.3%) and 46 males (10.7%) between January 10, 2022, and February 11, 2023, in Mashhad, Iran were evaluated to detect HPV and determine its genotypes. Cervical swabs and urine samples were collected from females and males, respectively. Viral DNA was extracted by using a CedExtra purification kit (cedbio, Iran) and viral genotypes were identified with a High + Low Papillomastrip kit (Operon, Spain). Mann Whitney U test and Chi-square test were accomplished for statistical analysis.

Result: From the total of 428 participants analyzed, the HPV test result was positive for 129 patients (30.1%) and negative for 299 people (69.9%). Among the participants, 115 female (30.1%) and 14 male (30.4%) were positive for HPV infection. The prevalence of HPV infection among the referring people was about 30%. The most common genotype identified was HPV-6 (10.3%), followed by HPV-16 (8.7%) and HPV-51 (7.7%), the second and third most common genotypes, respectively. Additionally, HPV-39 was detected at a frequency of 6.70%. HPV-11, HPV-61, HPV-91, and HPV-44 with a frequency of 1% were among the least genotypes identified among the patients.

Conclusion: In line with the results of this study, the prevalence of HPV genotypes in both genders is 30%. The results likely reflect differences in the prevalence of high-risk HPV genotypes, that are less common. Also, HPV-6 and HPV-16 genotypes that are covered by the vaccine had a significant prevalence. On the other hand, with the prevalence of HPV-51 and HPV-39 genotypes in infected people who are not covered by the Gardasil (quadrivalent) vaccine, there is a risk of related cancers in the future.

Background: Cervical squamous cell carcinoma (CSCC) is a prevalent gynecological malignancy worldwide. Current treatments for CSCC can impact fertility and cause long-term complications, underscoring the need for new therapeutic strategies. Oncolytic virotherapy has emerged as a promising option for cancer treatment. Previous research has demonstrated the oncolytic activity of the coxsackievirus B3 strain 2035 A (CVB3/2035A) against various tumor types. This study aims to evaluate the clinical viability of CVB3/2035A for CSCC treatment, focusing on its oncolytic effect in patient-derived CSCC organoids.

Methods: The oncolytic effects of CVB3/2035A were investigated using human CSCC cell lines in vitro and mouse xenograft models in vivo. Preliminary tests for tumor-selectivity were conducted on patient-derived CSCC tissue samples and compared to normal cervical tissues ex vivo. Three patient-derived CSCC organoid lines were developed and treated with CVB3/2035A alone and in combination with paclitaxel. Both cytotoxicity and virus replication were evaluated in vitro.

Results: CVB3/2035A exhibited significant cytotoxic effects in human CSCC cell lines and xenograft mouse models. The virus selectively induced oncolysis in patient-derived CSCC tissue samples while sparing normal cervical tissues ex vivo. In patient-derived CSCC organoids, which retained the immunohistological characteristics of the original tumors, CVB3/2035A also demonstrated significant cytotoxic effects and efficient replication, as evidenced by increased viral titers and presence of viral nucleic acids and proteins. Notably, the combination of CVB3/2035A and paclitaxel resulted in enhanced cytotoxicity and viral replication.

Conclusions: CVB3/2035A showed oncolytic activity in CSCC cell lines, xenografts, and patient-derived tissue cultures and organoids. Furthermore, the virus exhibited synergistic anti-tumor effects with paclitaxel against CSCC. These results suggest CVB3/2035A could serve as an alternative or adjunct to current CSCC chemotherapy regimens.

Background: Variant analysis of distinct HPV types is important from different aspects including epidemiology, pathogenicity, and evolution.

Methods: For this reason, the full sequence of the E6 and E7 genes of HPV 58 was examined in 130 HPV 58-infected cervical samples using PCR and sequencing.

Results: Our results revealed that three lineages A, B, and D were found in this study; among which the B lineage was more common (91.50%). About sublineages, all samples of the B lineage belonged to the B1 sublineage, and samples that were classified as the A and D lineages were found to belong to the A1 (0.77%), A2 (5.38%), A3 (1.50%), and D2 (0.77%) sublineages. No statistically significant differences were found between lineages and stages of disease or amino acid changes (P > 0.05).

Conclusion: Our results showed that lineage B, sublineage B1, was dominant in Iran. However, more studies with larger sample sizes from different parts of Iran are essential for assessing the pathogenicity risk of HPV 58 lineages in Iranian women with cervical cancer.